TYROTHRICIN

Tyrothricin is a polypeptide antibiotic mixture isolated from Bacillus brevis and consists of tyrocidines and gramicidins. Tyrothricin shows activity against bacteria, fungi and some viruses. Tyrothricin containing formulations are used in sore throat agents and in agents for the healing of infected superficial and small-area wounds[1].

Signaling Pathways >> Anti-infection >> Influenza Virus

Research Areas >> Infection

Signaling Pathways >> Anti-infection >> Fungal

Signaling Pathways >> Anti-infection >> Bacterial

Tyrothricin is a mixture of polypeptides, consisting of 50%-70% tyrocidines and 25%-50% gramicidins. The group of tyrocidines is basic, cyclic peptides, whereas the fraction of gramicidins is neutral, linear peptides. Besides physiological and essential L-amino acids, the components of Tyrothricin also contain D-amino acids[1]. Tyrothricin is produced by the gram-positive aerobic sporeforming bacterium Bacillus brevis (Strain ATCC 8185) during its sporulation phase via the nonribosomal pathway[1]. The efficacy spectrum of Tyrothricin mainly covers gram-positive but also several gram-negative bacteria. Corynebacteria and staphylococci show a broader range of Tyrothricin concentrations for inhibition (2-256 μg/mL). In contrast to the gramicidin fraction alone, Tyrothricin is able to inhibit all Staphylococcus strains at a maximum concentration of 128 μg/mL. Among the gram-negative organisms, gonococci and meningococci were the most sensitive germs (96 μg/mL)[1]. Tyrothricin exerts fungicidal effects on a variety of Candida species.Tyrothricin shows an anti-infectious activity against parainfluenza virus (type Sendai)[1].

In animal models using HSV type 1, a pre-incubation of the virus suspension with Tyrothricin could significantly decrease the lethality in mice. The effect could only be shown after a direct contact between Tyrothricin and the virus[1]. Nevertheless disruption of the integrity of eukaryotic membranes is observed at higher Tyrothricin concentrations in vitro. This effect is exemplified as hemolytic activity of Tyrothricin in in vitro studies and when applied to animals i.v.. In contrast to an intravenous (LD50 mouse: 3,7 mg/kg) and an intraperitoneal (LD50 mouse: 20-45 mg/kg) application the oral application is very well tolerated, as Tyrothricin is destroyed in the gastro-intestinal tract[1].

[1]. Lang C, et al. Tyrothricin--An underrated agent for the treatment of bacterial skin infections and superficial wounds? Pharmazie. 2016 Jun;71(6):299-305.

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>3 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>1500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

1200 ug/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - excitement Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

20 mg/kg/10D-I

TOXIC EFFECTS :

Blood - changes in cell count (unspecified) Blood - changes in spleen Related to Chronic Data - death

MUTATION DATA

TYPE OF TEST :

DNA adduct

TEST SYSTEM :

Bacteria - Escherichia coli

DOSE/DURATION :

25 umol/L

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 89,95,1981 *** REVIEWS *** TOXICOLOGY REVIEW ADENAE Advances in Enzymology and Related Subjects of Biochemistry. (New York, NY) V.1-28, 1941-66. For publisher information, see AERAAD. Volume(issue)/page/year: 4,153,1944